The contributions of motor learning and inhibitory balance to stroke recovery

运动学习和抑制平衡对中风恢复的贡献

基本信息

批准号：
8618364
负责人：
STEVEN R ZEILER
金额：
$ 19.2万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-15 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8618364
关键词：
Address Adult Affect Animal Model Animals Area Behavioral Caring Data Development Development Plans Dose Equilibrium Fluorescence Microscopy Fluoxetine Foundations Funding Genetic Genetic Models Genetically Engineered Mouse Goals Hour Human Immunofluorescence Immunologic In Vitro Interneurons Intervention Ion Channel Ischemic Stroke Laboratories Learning Leg Light Long-Term Care Medial Mediating Medicine Mentors Motor Mus Neuronal Plasticity Neurons Parvalbumins Patients Positioning Attribute Property Prozac Publishing Recovery Rehabilitation therapy Research Research Personnel Role Saline Stroke Survivors Techniques Technology Testing Therapeutic Time Training Training Programs Translational Research Wild Type Mouse Work acute stroke arm awake calbindin calretinin career career development clinically relevant cranium design disability human data in vivo innovation interest knowledge base motor impairment motor learning mouse model neurotransmission novel strategies optogenetics post stroke programs public health relevance research and development skills statistics stroke recovery stroke rehabilitation

项目摘要

Project Abstract My proposal describes a mentored research and career development plan designed to facilitate my transition to an independent clinician-researcher. During the proposed 5 year plan, I will 1) characterize and begin to mechanistically define a post-stroke period of time during which motor recovery is decreasingly sensitive to motor training and 2) develop my career, skills, and knowledge base as I address this interesting and clinically relevant problem. Notably in human patients, most recovery from motor impairment after stroke occurs in the first month and is currently not the focus of most rehabilitation that predominantly targets function through compensatory strategies. Animal models, which also show the existence of a period of heightened recovery early after stroke, provide the opportunity to test approaches to augment and prolong this period of heightened recovery. Using a mouse model of post-stroke motor recovery, I propose to further define the post-stroke sensitive period by describing how the timing and dose of motor retraining interact to affect motor recovery, how fluoxetine (a commonly used anti-depressant medicine) can modify the sensitive period, and how specific neuronal activity influences this sensitive period. Specific training goals include 1) further development of mouse models in which to study post-stroke recovery, 2) developing a foundation in behavioral statistics, 3) learning advanced fluorescence microscopy, 4) learning in vivo optogenetics (optically controlling neuronal activity in an awake, behaving mouse), 5) translational research strategies, 6) developing an independent program of post-stroke recovery research, and 7) how to obtain independent funding. There is an urgent need to develop innovative approaches to post-stroke rehabilitation because despite improvements in acute stroke care, up to sixty percent of stroke survivors suffer disability in arm or leg use, and up to one-third need placement in a longer term care facility. The training program and mentoring team that I have assembled will help to elucidate important recovery interventions, position me to exploit genetic models that impact neural plasticity, and use cutting edge technology to advance this work as I transition to my independent laboratory.

项目摘要我的建议描述了一项指导的研究和职业发展计划，旨在促进我的过渡到独立的临床医生研究员。在拟议的5年计划中，我将1）表征并开始机械机械地定义了中风后期，在此期间，电动机回收对运动训练以及2）在我解决这个有趣和临床的问题时，发展了我的职业，技能和知识基础相关问题。值得注意的是，在人类患者中，大多数在中风后从运动障碍中恢复了大多数。第一个月，目前不是主要针对通过的大多数康复的重点补偿策略。动物模型，这也表明了恢复时期的存在中风后的早期，提供了测试方法来增强和延长这一时期的机会恢复。我建议使用击球后运动恢复的鼠标模型，我建议进一步定义击球后通过描述电动机的时间和剂量如何相互作用以影响运动恢复的敏感周期，氟西汀（一种常用的抗抑郁药）如何改变敏感时期，以及如何特异性神经元活动会影响这个敏感时期。具体培训目标包括1）进一步发展在其中研究势后恢复的小鼠模型，2）在行为统计中建立基础，3）学习高级荧光显微镜，4）在体内学习学学学习（光学控制神经元醒着的活动，行为鼠标），5）翻译研究策略，6）开发独立的冲程后恢复研究计划，以及7）如何获得独立资金。迫切需要开发创新的中风后康复方法，因为尽管急性中风有所改善护理，多达60％的中风幸存者在手臂或腿部使用中遭受残疾，最多三分之一的需求安置在长期护理设施中。我组装的培训计划和指导团队将有助于阐明重要的恢复干预措施，将我定位为利用影响神经的遗传模型当我过渡到独立实验室时，可塑性并使用尖端技术来推进这项工作。